Project Summary R01 AG058571 Type 2 diabetes, characterized by insulin resistance in peripheral tissues such as skeletal muscle, increases AD risk. However, it is unclear whether there is a similar, or stronger, relationship between insulin resistance in the brain and AD. The goal of the proposed administrative supplement to Look AHEAD-MIND, while within the original scope, is to further unravel molecular pathways linking the intensive lifestyle intervention to the development of cognitive impairment by examining neural-derived blood exosome biomarkers for brain insulin resistance and Alzheimer's disease (AD) pathologies.